Glucose-dependent insulinotropic polypeptide regulates dipeptide absorption in mouse jejunum
| Autor: | John H. Schwartz, Steven Coon, Satish K. Singh, Vazhaikkurichi M. Rajendran, Lisa I. Jepeal |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Physiology Hormones and Signaling Gastric Inhibitory Polypeptide Tripeptide Absorption Tissue Culture Techniques Jejunum Pathogenesis Mice Gastric inhibitory polypeptide Glucagon-Like Peptide 1 Physiology (medical) Internal medicine medicine Animals Mice Knockout Cephalexin Messenger RNA Hepatology Ussing chamber biology digestive oral and skin physiology Gastroenterology Dipeptides Glucagon-like peptide-1 Anti-Bacterial Agents Endocrinology medicine.anatomical_structure Gene Expression Regulation biology.protein Antibody hormones hormone substitutes and hormone antagonists |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 305:G678-G684 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00098.2013 |
| Popis: | Glucose-dependent insulinotropic polypeptide (GIP) secreted from jejunal mucosal K cells augments insulin secretion and plays a critical role in the pathogenesis of obesity and Type 2 diabetes mellitus. In recent studies, we have shown GIP directly activates Na-glucose cotransporter-1 (SGLT1) and enhances glucose absorption in mouse jejunum. It is not known whether GIP would also regulate other intestinal nutrient absorptive processes. The present study investigated the effect of GIP on proton-peptide cotransporter-1 (PepT1) that mediates di- and tripeptide absorption as well as peptidomimetic drugs. Immunohistochemistry studies localized both GIP receptor (GIPR) and PepT1 proteins on the basolateral and apical membranes of normal mouse jejunum, respectively. Anti-GIPR antibody detected 50-, 55-, 65-, and 70-kDa proteins, whereas anti-PepT1 detected a 70-kDa proteins in mucosal homogenates of mouse jejunum. RT-PCR analyses established the expression of GIPR- and PepT1-specific mRNA in mucosal cells of mouse jejunum. Absorption of Gly-Sar (a nondigestible dipeptide) measured under voltage-clamp conditions revealed that the imposed mucosal H+ gradient-enhanced Gly-Sar absorption as an evidence for the presence of PepT1-mediated H+:Gly-Sar cotransport on the apical membranes of mouse jejunum. H+:Gly-Sar absorption was completely inhibited by cephalexin (a competitive inhibitor of PepT1) and was activated by GIP. The GIP-activated Gly-Sar absorption was completely inhibited by RP-cAMP (a cAMP antagonist). In contrast to GIP, the ileal L cell secreting glucagon-like peptide-1 (GLP-1) did not affect the H+:Gly-Sar absorption in mouse jejunum. We conclude from these observations that GIP, but not GLP-1, directly activates PepT1 activity by a cAMP-dependent signaling pathway in jejunum. |
| Databáze: | OpenAIRE |
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